Voltage dependence of the pattern and frequency of discrete Ca2+ release events after brief repriming in frog skeletal muscle

Applying a brief repolarizing pre-pulse to a depolarized frog skeletal muscle fiber restores a small fraction of the transverse tubule membrane voltage sensors from the inactivated state. During a subsequent depolarizing test pulse we detected brief, highly localized elevations of myoplasmic Ca²⁺ concentration (Ca²⁺ “sparks”) initiated by restored voltage sensors in individual triads at all test pulse voltages. The latency histogram of these events gives the gating pattern of the sarcoplasmic reticulum (SR) calcium release channels controlled by the restored voltage sensors. Both event frequency and clustering of events near the start of the test pulse increase with test pulse depolarization. The macroscopic SR calcium release waveform, obtained from the spark latency histogram and the estimated open time of the channel or channels underlying a spark, exhibits an early peak and rapid marked decline during large depolarizations. For smaller depolarizations, the release waveform exhibits a smaller peak and a slower decline. However, the mean use time and mean amplitude of the individual sparks are quite similar at all test depolarizations and at all times during a given depolarization, indicating that the channel open times and conductances underlying sparks are essentially independent of voltage. Thus, the voltage dependence of SR Ca²⁺ release is due to changes in the frequency and pattern of occurrence of individual, voltage-independent, discrete release events.     

Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor

Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction.     

Effectiveness and Prognostic Factors of Radiotherapy for Painful Plantar Heel Spurs

BACKGROUND AND PURPOSE: The efficacy of radiation treatment (RT) for plantar heel pain has been reported repeatedly. Yet, the results referring to the pain relief rate, to long-term effects and prognostic factors are not consistent. In this paper, the effectiveness (pain relief rate and long-term results) and prognostic factors of RT for plantar heel pain have been investigated. PATIENTS AND METHODS: From January 2000 to October 2000, 62 patients (73 heels) with painful plantar heel spurs and a minimum pain history of 3 months were treated and evaluated in a prospective study. Mean age was 54 years (range 28-84 years). All patients were treated with a total dose of 5 Gy in seven fractions (= one series), given twice a week at a single-dose sequence of 0.25-0.25-0.5-1.0-1.0-1.0-1.0 Gy (10-MV photons, source-skin distance [SSD] 100 cm, direct portal, field size 12 x 17 cm). The mean duration of heel pain before RT was 26 weeks (= 6.5 months; range 3-120 months). By means of a visual analog scale (VAS) the patients had to self-assess the quantity of their heel pain once before, three times during and four times after RT at a longterm median follow-up of 28 and 40 months. Additionally, the patients had to assess their mechanical heel stress extent during RT. Effectiveness was estimated according to the patients' judgment of pain reduction. RESULTS: A significant reduction of heel pain extent measured by VAS has been observed already during the RT series (before RT: 6.3 +/- 1.5 vs. 3.8 +/- 2.1 at the end of RT; p < 0.001). 6 weeks after RT (FU 1) pain reduction (> 20%) was achieved in 60 heels (82.3%; n = 73), in 64 heels (91.4%; n = 70) after a mean follow-up of 28 months (FU 2), and in 61 heels (89.7%; n = 68) after a mean follow-up of 40 months (FU 3), respectively. Sufficient pain relief (> 80% compared to initial extent) was observed in 18/73 heels (24.6%) at FU 1 (FU 2: 42/70; 60.0%; FU 3: 37/68; 54.4%), including 13/73 heels (17.8%) with complete pain relief (FU 2: 39/70; 55.7%; FU 3: 36/68; 52.9%). Partial improvement (50-80% pain reduction) was observed in 27/73 heels (37.0%) at FU 1 (FU 2: 14/70; 20.0%; FU 3: 15/68; 22.1%), and minor partial improvement (20-50% pain reduction) in 15/73 heels (20.5%) at FU 1 (FU 2: 8/70; 11.4%; FU 3: 9/68; 13.2%), respectively. No change was seen in 13/73 heels (17.8%) at FU 1 (FU 2: 6/70; 8.6%; FU 3: 7/68; 10.3%). Older patients (p = 0.04) and patients who avoided heel stress during the period of RT (p < 0.01) demonstrated a better short-term response (FU 1); both effects were lost 28 and 40 months after RT. Moreover, significant differences in the extent of heel pain reduction by RT were observed in dependence on previous pain duration (at FU 2-3). CONCLUSION: The results confirm the high efficacy of RT in painful plantar spur and add new aspects to formerly published data concerning the time course of changes in heel pain reduction. Pain relief can be expected during and shortly after RT. In addition, the initial success can be transformed into effective long-term results > 2 years after RT; however, further improvement is not to be expected. As a new prognostic factor, the reduction of mechanical heel stress during RT may ameliorate the short-term results, whereas short heel pain history improves the long-term results. Especially for older patients, RT should be taken into consideration as primary treatment.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Receptor-mediated lipoprotein transport in laying hens

In laying hens, VLDL and vitellogenin (VTG) are secreted by the liver and eventually taken up by the growing oocyte via receptor-mediated endocytosis. Both macromolecules bind to the same receptor, termed the VLDL/VTG receptor, localized on the oocyte plasma membrane. Once taken up by the growing zygote, apolipoprotein B, the major protein constituent of VLDL, is proteolytically cleaved by a chicken-specific cathepsin-D. Systemic cholesterol homeostasis in the chicken is maintained by expressing a different apoprotein B-specific receptor in somatic cells, which in terms of its function is very similar to the mammalian LDL receptor. The phenotype of the Restricted Ovulator hen, characterized by hereditary hyperlipidemia and the absence of egg laying, was identified as a lack of expression of functional VLDL/VTG receptors in the oocytes without affecting somatic apoprotein B receptors.     

The spring-back phenomenon: does the final position of the nipple areola complex correspond to the pre-operative markings in reduction mammoplasty?

This study investigates whether tissue recoil or patient intrinsic factors influence the final position of the nipple areola complex (NAC) after reduction mammoplasty. The age, pre-operative ptosis, BMI and weight of the tissue resected were recorded as patient intrinsic factors in 37 patients undergoing reduction mammoplasty. The “spring-back” value was defined as the distance from the sternal notch to a nipple landmark on the breast meridian with the patient sitting up, minus the same measurement repeated with the patient recumbent to eliminate the pull of gravity on the breast. Spring back was measured pre-operatively for the nipple and nipple mark then post-operative for the nipple. The difference in centimeters between the final post-operative distance from the sternal notch to the nipple and the level intended by the pre-operative nipple mark was termed the “judgment error.” The final position of the post-operative nipple and the judgment error was compared to the spring-back values and patient intrinsic factors. Pre-operative ptosis was statistically related to increasing patient BMI and mass of tissue resected per breast. Pre-operative spring-back values for the nipple increased with increasing ptosis, BMI and decreasing age. Spring-back values were greater in the lower pole of the breast than in the upper pole. The final position of the nipple was higher than the pre-operative mark in 65% of cases, lower in 8% and as marked in 27% of cases. The post-operative NAC was, on average, 0.6 cm higher than planned pre-operatively. The post-operative distance from the sternal notch to the nipple increased with increasing pre-operative ptosis, mass of breast tissue resected per breast and all three spring-back values. The difference between the level of the pre-operative mark and the final nipple position showed a weak correlation with post-operative spring-back values. The parameters of ptosis, BMI, weight of tissue resected per breast and pre-operative nipple spring back reflect body habitus and breast size. Spring-back values vary between the upper and lower pole of the breast. The final NAC position was higher than that intended at pre-operative marking in the majority of cases. The surgeon instinctively marks the nipple lower in patients with greater pre-operative ptosis and in whom a larger resection is anticipated. Judgment error did not relate to intrinsic factors nor to pre-operative spring-back values; hence, these parameters cannot be applied as predictive tools for more accurate pre-operative marking of the nipple position. This study suggests that the pre-operative nipple mark should be placed, with the patient sitting up, at least 23 cm from the sternal notch and 0.6 cm lower than the final position estimated using the inframammary crease as a landmark. An invited commentary on this paper is available at .     

Hemodialysis vascular access: how do practice patterns affect outcomes?

There are significant international differences in the type of vascular accesses that are routinely used in the hemodialysis population. Most U.S. hemodialysis patients dialyze with grafts or catheters, while most European and Japanese patients dialyze with the preferable native arteriovenous (A-V) fistulae. Recent analyses suggest that several practice patterns that can be significantly affected by nephrology nurses may help increase both the use of native A-V fistulae and vascular access longevity in the U.S.